This project will study the effect of a substance isolated from the hypothalamus which has the ability to inhibit the release of free fatty acids in response to norepinephrine both in the intact animal and in an in vitro sytem. This hypothalamic factor (HF) also has a central action and when administered to mice caused an elevation of brain catecholamines norepinephrine (NE) and dopamine )DA); it also has the ability to protect against the toxicityof DL-amphetamine (a sympatheomimetic agent) and to reverse the effect of this drug on brain gamma-amino butyric acid (GABA) levels. We propose to study the effect of HF on CNS distribution of such amino acids as glycine, glutamic and aspartic acids which have been implicated in neurotransmission. Enzymes associated with GABA synthesis and metabolism will be studied, as well as enzymes associated with the synthesis of norepinephrine and dopamine, e.g. tyrosine hydroxylase, which is the rate limiting step in the biosynthetic pathway of the catecholamines. It is hoped to associate the role HF in lipid metabolism with its action on neurotransmitters.